The objectives of the proposed research are to investigate the role of mitochondria and, specifically, mitochondrial monoamine oxidase (MAO) in regulating biogenic amine metabolism. Biochemical data recently obtained in this laboratory support the idea that MAO activity and the flow of electrons along the respiratory path are integrated and may provide a mechanism regulating the level of intracellular biogenic amines which is coupled to cellular energy conservation or utilization. Ultra-structural studies during these reactions show close apposition or fusion of the inner and outer mitochondrial membranes. The fact that the storage and uptake of biogenic amines are ATP-dependent further suggests that mitochondrial function is involved, indirectly if not directly, in these processes. Rat liver mitochondria will be used as a model system for these studies and will provide a basis for comparing mitochondria from cells or tissues known to store amines such as blood platelets, adrenal medulla, and brain. In addition, mitochondria from cell types shown to have low or no MAO activities will be studied. Such mitochondria can be found and isolated from cells of major biomedical interest, Morris hepatomas, Ascites tumor cells, and blood platelets from schizophrenic patients. MAO activities in the isolated mitochondria will be measured using a variety of substrates and the effects of MAO inhibitors on both MAO activity and mitochondrial respiration will be measured. The converse, the effect of respiratory inhibitors on MAO activity, will also be assayed. The localization and presence or absence of MAO in these mitochondria will also be investigated using electron microscopy by applying, in addition to routine thin-sectioning techniques, cytochemical, ferritin-antibody tagging, and freeze-fracturing methods.